Document Detail


Protective effect of vinconate on ischemia-induced neuronal damage in the rat hippocampus.
MedLine Citation:
PMID:  1468504     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The protective effect of vinconate, a vinca alkaloid derivative, on ischemia-induced neuronal damage was investigated using a model of rat forebrain ischemia caused by occlusion of four vessels. Hippocampal cell loss was observed histologically and neurochemically 5 days after 10 min of ischemia. Treatment with vinconate (50 and 200 mg/kg i.p.) before cerebral ischemia significantly suppressed neuronal cell loss in the hippocampal CA1 region and the decrease in the content of neuroactive amino acids in the hippocampus. The release of neuroactive amino acids in the hippocampus was significantly increased by cerebral ischemia. Pretreatment with vinconate (50 and 200 mg/kg i.p.) significantly attenuated the increased release of glutamic acid and aspartic acid, but not the release of gamma-aminobutyric acid (GABA), taurine and glycine. This suppressive effect of vinconate was antagonized by scopolamine (10(-5) M). The addition of vinconate (10(-11)-10(-4) M) had no effect on the binding of [3H]MK-801. These results indicate that pretreatment with vinconate attenuates the ischemia-induced release of excitatory amino acids into the extracellular space of the hippocampus via the stimulation of presynaptic muscarinic acetylcholine receptors. The present results also suggest that this suppressive effect of vinconate on the release of excitatory amino acids (glutamic acid and aspartic acid) may play a crucial role in the protective action of this agent against ischemia-induced neuronal damage in the hippocampus.
Authors:
T Iino; M Katsura; K Kuriyama
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  European journal of pharmacology     Volume:  224     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:  1992 Dec 
Date Detail:
Created Date:  1993-01-28     Completed Date:  1993-01-28     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  117-24     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, Kyoto Prefectural University of Medicine, Japan.
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MeSH Terms
Descriptor/Qualifier:
Amino Acids / metabolism*
Animals
Brain Ischemia / metabolism*,  pathology
Dizocilpine Maleate / metabolism
Drug Interactions
Hippocampus / drug effects,  metabolism*,  pathology
Male
Neurons / drug effects*,  metabolism
Rats
Rats, Wistar
Scopolamine / pharmacology
Synaptic Membranes / drug effects,  metabolism
Vinca Alkaloids / pharmacology*
Chemical
Reg. No./Substance:
0/Amino Acids; 0/Vinca Alkaloids; 51-34-3/Scopolamine; 70704-03-9/vinconate; 77086-22-7/Dizocilpine Maleate

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